Investigations will continue which are directed at the delineation of the mechanisms by which insulin and glucagon effect the short-term and long-term regulation of the activities of acetyl-CoA carboxylase, fatty acid synthetase and Beta-hydroxy-Beta-methylglutaryl coenzyme A (HMG-CoA) reductase in mammalian liver. These studies will be carried out with isolated cells, tissue cultures and whole animals. Studies on acetyl-CoA carboxylase will concentrate initially on the mechanism by which glucagon decreases fatty acid synthesis in 1-hour incubations of isolated hepatocytes. Studies will also be carried out which are directed towards the purification to homogeneity of a soluble protein of rat liver that inhibits acetyl-CoA carboxylase activity. The physiological significance of this protein will then be determined. Investigations on rat liver fatty acid synthetase will concentrate on the purification to homogeneity of the mRNA for this enzyme. When this is accomplished, attempts will be made to synthesize cDNA to this mRNA. Studies will also be initiated on the mechanism by which insulin regulates the rate of synthesis of mRNA for this protein. Studies on HMG-CoA reductase will concentrate on the production of monospecific antibody to this enzyme. When this goal is achieved, attempts will be made to delineate in further detail the mechanisms by which nutritional and hormonal factors regulate the activity of this enzyme. Included in these studies will be ones on the mechanism by which insulin regulates the activity of this enzyme. We will also, as a part of these studies, attempt to isolate and translate the mRNA for HMG-CoA reductase.